SPOP loss of function protects against tauopathy.

ABSTRACT: The pathological accumulation of the microtubule binding protein tau drives age-related neurodegeneration in a variety of disorders, collectively called tauopathies. In the most common tauopathy, Alzheimer's disease (AD), the accumulation of pathological tau strongly correlates with cognitive decline. The underlying molecular mechanisms that drive neurodegeneration in tauopathies remain incompletely understood and no effective disease modifying pharmacological interventions currently exist. Here, we show that tau toxicity depends on the highly conserved nuclear E3 ubiquitin ligase adaptor protein SPOP in a Caenorhabditis elegans model of tauopathy. Loss of function mutations in the C. elegans spop-1 gene significantly improves behavioral deficits in tau transgenic animals, wh

SUBMITTER: Eck RJ 

PROVIDER: S-EPMC9910588 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature